Excitation of nerve

Zhang, SJ and Jackson, MB (1995) GABAa receptor activation and the excitability of nerve terminals in the rat posterior pituitary. /. Physiol. (Lond.) 483 583-595. 

Calcium is the most abundant body constituent (approx. 2% of body weight). It controls excitability of nerves and muscles and regulates permeability of cell membranes. It act as intracellular messenger for hormones and autacoids and help in coagulation of blood. 

We recently proposed a completely electronic model for the excitability of nerve membranes that is based on the assumption of electron-donating, electron-accepting, and electron-storing properties of macromolecules or of protein-lipid complexes which constitute the ionic channels of the nerve membrane (63). This model, which is based on simple physical concepts with easily defined parameters, reproduces the empirical Hodkgin-Huxley equations rather well and also explains how different types of drugs may work on nerves. The model is easily extended to other excitable complexes like the receptor protein complex at nerve synapses and the rodopsin molecules in the retina. Nor is it inconceivable to build a model for the function of smell that is based on electronic triggering of ionic channels which are affected by molecules adsorbed onto or dis-... 

Many substances of widely different chemical structure abolish the excitability of nerve fibers on local application in concentrations that do not cause permanent injury and that may not affect other tissues. Sensory nerve fibers are most susceptible, so that these agents produce a selective sensory paralysis, which is utilized especially to suppress the pain of surgical operation. This property was first discovered in cocaine, but because of its toxicity and addiction liability, it has been largely displaced by synthetic chemicals. The oldest of these, procaine (novocaine), is still the most widely used. Its relatively low toxicity renders it especially useful for injections, but it is not readily absorbed from intact mucous membranes and is therefore not very effective for them. Many of its chemical derivatives are also used. They differ in penetration, toxicity, irritation, and local injury as well as in duration of action and potency. Absolute potency is not so important for practical use as is its balance with the other qualities. If cocaine is absorbed in sufficient quantity, it produces complex systemic actions, involving stimulation and paralysis of various parts of the CNS. These are mainly of toxicological and scientific interest. Its continued use leads to the formation of a habit, resembling morphinism. This is not the case with the other local anesthetics. 

We may extrapolate from these basic considerations in two ways. We may evaluate the extracellular electric gradients associated with intrinsic or imposed tissue fields against the magnitude of the gradients in the membrane potential, both in resting conditions and in association with modification of the membrane potential during synaptic excitation. In this way, we may appraise the probability of direct effects of extracellular tissue fields in excitation of nerve cells. A second approach will consider the observed biological sensitivities to these fields. This will lead to the crux of our current dilemma. A... 

Q12 Hypocalcaemia increases the excitability of nerve and muscle cells. It is associated with reduction of the threshold potential necessary for initiation of nerve impulses, and consequently cell excitation occurs following a slight stimulus. The resulting symptoms include prolonged muscle spasms, which can particularly affect the face and limbs, hyper-reflexia, clonic-tonic convulsions and laryngeal spasm, which could cause asphyxia. 

Of the 25 animal phyla, almost half are worms. Thus, it is not at all surprising that some worms contain toxins. The nemertines are a phylum of over 800 known species which resemble flatworms but are active predators on crustaceans and other worms. This phylum is exceptionally toxic among the various worm phyla. The Heteronemertine side possesses peptide toxins which appear to be only defensive, as these animals have no means of injecting a venom. The peptides include neurotoxins, which enhance excitability of nerve membranes, and cytolysins, which permeabilize and destroy cell membranes. Members of the Hoplonemertine class inject a venom into their prey using a mineralized stylet located in their proboscis, which is also used to immobilize the prey. Their toxins are alkaloids similar to nicotine which in minute amounts paralyze crustaceans and annelid worms and primarily activate nicotinic acetylcholine receptors. Another well-known worm toxin is nereistoxin, a disulfide-containing alkaloid which also binds to nicotinic... 

Because the processes of excitation are largely dissipative (i.e., the flow of ions down existing electrochemical gradients and the use of chemical bond energy to restore the ionic gradients), a net evolution of heat would be expected. This evolution is observed, but measurements of the heat associated with excitation of nerve fibers (24) or electric organs (25) indicate three distinct phases in the heat flow during an action potential ... 

Potassium appears to perform many of the same functions inside the cell that sodium performs in the plasma and interstitial fluid. Potassium, in various ways 1) regulates the maintenance of the osmotic equilibrium of body fluids 2) acts as an available base to neutralize acids 3) maintains an ionic balance between potassium, sodium, calcium, and magnesium, which in turn affects capillary and cell functions and the excitability of nerves and muscles 4) maintains correct water balance in the body and 5) acts as a cofactor in several enzyme systems, including those used for energy transfer and utilization, protein synthesis, and carbohydrate metabolism (Oberleas et al. 

The distinctive feature of a modulator is that it originates from nonsynaptic sites, yet influences the excitability of nerve cells. Substances such as CO2 and ammonia, arising from active neurons or glia, are potential modulators through nonsynaptic actions. Similarly, circulating steroid hormones, steroids produced in the nervous system (i.e., neurosteroids, locally released adenosine, other purines, eicosanoids, and NO are regarded as modulators (see below). 

Local anesthetics decrease the excitability of nerve cells without affecting the resting potential. Because the action potential, or the ability of nerve cells to be excited, seems to be associated with the movement of sodium ions across the nerve membranes, anything that interferes with the movement of these ions interferes with cell excitability. For this reason, many hypotheses have been suggested to explain how local anesthetics regulate the changes in sodium permeability that underlie the nerve impulse. These hypotheses include direct action on ionic channels that interferes with ionic fluxes and interaction with phospholipids and calcium that reduces... 

However, macromolecular moieties (cytoskeletal protein-like) located at the inner surface of nerve membranes seem to have an important role in stabilizing the membrane as well as maintaining membrane potential, especially for maintaining excitability of nerve fibers. According to Tasaki et... 

The second level (1 mA) of 50/60 Hz is due to the direct electric excitation of nerves. The level increases as frequency is increased above 1 kHz (Figure 10.18). For example, 10 mA at 100 kHz is without perception, but temperature rise caused by the current may then be a limiting factor. Interpersonal variations... 

The second level (1 mA) is due to the direct electric excitation of nerve endings, which must be a function of the local current (density). The electric current threshold of perception with firm hand grip contact and contact area several square centimeters, is around 1 mA. Threshold current has a surprisingly small dependence on contact area. The reason for this is mentioned previously in the chapter on DC perception. With a small area contact around... 

Cole, K.S., 1934. Alternating current conductance and direct current excitation of nerve. Science 79, 164—165. Cole, K.S., 1940. Permeability and impermeability of cell membranes for ions. Cold Spring Harb. Symp. 

Potassium has an important role in metabolism as evidenced by the close relationship between cell growth and breakdown and potassium accumulation and loss (see Chapter 3). The excitability of nerve tissue and the transmission of impulses is profoundly influenced by the concentration of potassium in the cells and extracellular fluids. Potassium plays an important role in the contractility of all types of muscle. Paralysis of striated muscle occurs when the level of serum potassium is less than 2.05 to 2.56 meq. per liter. Smooth muscle is also affected in potassium deficiency, and paralytic ileus may result. The activity of cardiac muscle is affected... 

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